The proposed studies are to examine the regulation of collagen synthesis by embryonic chick corneas and to determine the possible defects, on a molecular basis, involved in heritable ocular diseases in humans such as keratoconus, macular dystrophy, granular dystrophy, etc. Different collagen types in corneas will be purified by neutral salt fractionation and characterized with peptide-map analysis. Also, the purified collagen types will be used to produce specific antibodies in rabbits, and quantitative procedures such as rocket immunoelectrophoresis and/or radioimmune assay will be set up to measure the rates of synthesis of various specific collagen types of matrix-free corneal cells isolated from embryonic chick corneas at different stages of development. Also, the kinetics for secretion of procollagen will be examined in order to assign various rate limiting steps to the corneal cells. The effects of cis-hydroxyproline, a proline analogue, on the synthesis of procollagen by the corneal cells and the toxicity of the analogue on these cells will be examined in order to set up a model system to investigate the effect of the analogue on collagen synthesis in corneas and the possibilities for using this analogue as a pharmaceutical agent to treat diseases having an overproduction of collagen, such as in wounded corneas. The techniques introduced and developed here will be applied to characterize the collagen synthesized by cultured corneal cells from patients with corneal diseases and to determine the possible defects at the molecular level which account for these disorders.